title: Vancomycin MIC as a predictor of outcome in MRSA bacteraemia in the UK context.
abstract: Received 29 November 2012; returned 20 February 2013; revised 16 May 2013; accepted 18 May 2013 OBJECTIVES: Raised vancomycin MICs have been associated with poor outcomes for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in the USA and mainland Europe. We investigated if this also applies in the UK, where EMRSA-15 (clonal complex 22) dominates.
  
  
  METHODS
  Isolates from UK patients receiving vancomycin therapy for MRSA bacteraemia in 2008-10 were collected, along with clinical details. Outcomes (i.e. patient survival or bacteraemia resolution) were reported 28 days after vancomycin therapy ended. The relationship between clinical outcome and MIC--as determined by CLSI and BSAC agar dilution methods--was assessed.
  
  
  RESULTS
  Among 228 MRSA bacteraemias, 82% were caused by EMRSA-15; 65% of the patients were male and the median age was 70.5 years. MICs correlated between methods, but CLSI agar dilution testing gave a mode at 1 mg/L with only 12% of results either side, whereas the BSAC method gave a mode straddling 0.7-1 mg/L with <4% outliers. Twenty-three percent of patients died, with MRSA contributory in half; another 17% had unresolved bacteraemia at 28 days. Neither death nor unresolved bacteraemia was significantly associated with higher vancomycin MICs by either method. Rifampicin co-therapy had no quantifiable effect on outcome. The patient's age was the only significant correlate of patient outcome (P < 0.01); the underlying medical condition of the patient was important for the resolution of bacteraemia (P < 0.01), though not for overall mortality.
  
  
  CONCLUSIONS
  Subtle vancomycin MIC differences did not correlate with worse outcomes for vancomycin monotherapy or for vancomycin/rifampicin co-therapy in MRSA bacteraemia. Regardless of the exact MIC-outcome relationship, detecting such small MIC differences seems unlikely to be reliable in routine laboratories.
authors.affiliation: Public Health England-Colindale, London NW9 5EQ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Hope
authors.forename: R M
authors.initials: RM
authors.lastname: Blackburn
authors.forename: N Q
authors.initials: NQ
authors.lastname: Verlander
authors.forename: A P
authors.initials: AP
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Kearns
authors.forename: R
authors.initials: R
authors.lastname: Hill
authors.forename: S
authors.initials: S
authors.lastname: Hopkins
authors.forename: E
authors.initials: E
authors.lastname: Sheridan
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011379:Prognosis; D012293:Rifampin / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D016896:Treatment Outcome; D006113:United Kingdom; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D012293:Rifampin
keywords: BSAC; CLSI; EMRSA-15; mortality